Abstract
Kinases are critical intracellular signaling proteins. To better understand kinase-mediated signal transduction, a large-scale human–yeast genetic interaction screen was performed. Among 597 human kinase genes tested, 28 displayed strong toxicity in yeast when overexpressed. En masse transformation of these toxic kinase genes into 4653 homozygous diploid yeast deletion mutants followed by barcode sequencing identified yeast toxicity modifiers and thus their human orthologs. Subsequent network analyses and functional grouping revealed that the 28 kinases and their 676 interaction partners (corresponding to a total of 969 genetic interactions) are enriched in cell death and survival (34%), small-molecule biochemistry (18%) and molecular transport (11%), among others. In the subnetwork analyses, a few kinases were commonly associated with glioma, cell migration and cell death/survival. Our analysis enabled the creation of a first draft of the kinase genetic interactome network and identified multiple drug targets for inflammatory diseases and cancer, in which deregulated kinase signaling plays a pathogenic role.
Highlights
Kinases catalyze the transfer of phosphate groups from high-energy phosphate-donating molecules to specific substrates via a process known as phosphorylation
A “modifier genetics” approach was applied to these human kinases, in which kinase toxicity was modified by specific deletion of yeast genes
The toxicity modifiers in which kinase toxicity was modified by specific deletion of yeast genes
Summary
Kinases catalyze the transfer of phosphate groups from high-energy phosphate-donating molecules to specific substrates via a process known as phosphorylation. Lipids and carbohydrates can be substrates of the phosphorylation process. The phosphorylation states of these molecules affect their activity and ability to bind other molecules, thereby regulating cell signaling, metabolism and other important cellular pathways. Kinases constitute a major component of intracellular. As the single most important protein family in signal transduction, they were extensively exploited as a drug target for a variety of cancers and immune/inflammatory disorders [1,2]. The elucidation of numerous kinase-signaling pathways and the crosstalk between them remains a formidable challenge, necessitating intense investigations currently in progress worldwide
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
